title: Improved wound healing of postischemic cutaneous flaps with the use of bone marrow-derived stem cells.
abstract: OBJECTIVE
  To determine if the intravascular delivery of mesenchymal stem cells improves wound healing and blood perfusion to postischemic cutaneous flap tissues.
  
  
  METHODS
  Randomized controlled study.
  
  
  METHODS
  A murine model of a cutaneous flap was created based on the inferior epigastric vessels. Mice (n = 14) underwent 3.5 hours of ischemia followed by reperfusion. Bone marrow stromal cells (BMSCs) 1 × 10(6) were injected intravenously. Wound healing was then assessed measuring percent flap necrosis, flap perfusion, and tensile strength of the flap after a period of 14 days. Localization of BMSCs was determined with radiolabeled and fluorescent labeled BMSCs.
  
  
  RESULTS
  Postischemic cutaneous flap tissues treated with BMSCs demonstrated significantly less necrosis than control flaps (P <0.01). Beginning on postoperative day 5, BMSC-treated flaps demonstrated greater blood perfusion than untreated flaps (P <0.01). Tensile strength of BMSC-treated cutaneous flaps was significantly higher (P <0.01), with a mean strength of 283.4 ± 28.4 N/m than control flaps with a mean of 122.4 ± 23.5 N/m. Radiolabeled BMSCs localized to postischemic flaps compared to untreated tissues (P = 0.001). Fluorescent microscopy revealed incorporation of BMSCs into endothelial and epithelial tissues of postischemic flaps.
  
  
  CONCLUSIONS
  This study demonstrates that the intravascular delivery of BMSCs increases wound healing and promotes flap survival following ischemia-reperfusion injury of cutaneous tissue flaps.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, LSUH-S, Shreveport, Louisiana, U.S.A.
authors.forename: Melissa
authors.initials: M
authors.lastname: Hu
authors.forename: David
authors.initials: D
authors.lastname: Ludlow
authors.forename: J Steven
authors.initials: JS
authors.lastname: Alexander
authors.forename: Jerry
authors.initials: J
authors.lastname: McLarty
authors.forename: Timothy
authors.initials: T
authors.lastname: Lian
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology; D004195:Disease Models, Animal; D006085:Graft Survival; D007262:Infusions, Intravenous; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis / Q000473:pathology; D011897:Random Allocation; D012039:Regional Blood Flow / Q000502:physiology; D015427:Reperfusion Injury / Q000473:pathology / Q000628:therapy*; D018570:Risk Assessment; D018709:Statistics, Nonparametric; D013524:Surgical Flaps / Q000098:blood supply / Q000473:pathology*; D013718:Tensile Strength; D016896:Treatment Outcome; D014945:Wound Healing / Q000502:physiology*
keywords: Bone marrow stromal cells; Level of Evidence: NA; cutaneous flaps; free tissue transfer; ischemia; stem cells; wound healing